The present invention relates to novel methods and articles of manufacture which are packages containing compositions useful for treating symptoms associated with the menopause. More particularly, the present invention is directed to relieving or preventing menopausal or perimenopausal symptoms in the female human by use of a stepwise, graded, sequential, natural estrogen-progestogen regimen.
Treatment of the menopause has been focused largely on the distressing symptoms associated therewith, e.g., hot flushes (or flashes), headache, insomnia, fatigue, nervousness, depression, joint pains, and so forth.
More serious symptoms are recurrent cysto-urethritis; dysparunia and vaginal atrophy; and menorrhagia. Perhaps the most serious associated biological change is osteoporosis, a process which begins during menopause and continues in the post-menopausal years. This bone-degeneration is gradual, but irreversible; hip fractures, which are associated with substantial mortality risk, are common among post-menopausal women.
The administration of female hormones has been recommended since the menopause can be regarded as a deficiency state with respect to the production of those hormones. Estrogens, both synthetic and natural, have been used. Some efforts to replace both types of deficient hormones, namely, estrogen and progestogen, have relied on the commonly available oral contraceptive regimens. These regimens do not approach the physiological estrogen and progestogen levels of the natural ovarian cycle, since they are directed to disrupting it and may be responsible for some intolerance of the treatment because of relative excesses of the components.
Attempts to mimic the natural level of hormones in the cycle by administration of estrogen and/or progestogen in amounts presumably necessary to restore the hormonal concentrations to premenopausal levels are well known, (See, e.g., U.S. Pat. No. 3,733,407). Several regimens are, in fact, marketed, e.g., Cyclo-Progynova, (Schering); Premarin (Ayerst) and Prempak (Ayerst).
The present invention, provides a "rest" period wherein no hormones are administered, requires the use of natural, rather than synthetic, estrogen, and includes the use of a styptic progestogen, e.g., norethisterone, and thus avoids the problems associated with constant dosage and synthetic materials.